beta-(2-methylpiperidino) ethylemethylphenylamine salt of penicillin



UNITED STATES PATENT OFFICE 3- (2-METHYLPIPERIDINO) ETHYLMETHYL- PHENYLAMINE SALT OF PENICILLIN Harley W. Rhodehamel, Jr., Indianapolis, Ind., assignor to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana No Drawing. Application February 13, 1952, Serial No. 271,435

2 Claims. (Cl. 260-239.1)

This invention relates to a novel penicillin salt dino) ethylmethylphenylamine dihydrochloride in and the preparation thereof. 5 ml. of water. The mixture is cooled and stirred I have discovered that ,6-(2-methylpiperidino) occasionally whereupon the slightly soluble 8-(2- ethylmethylphenylamine or its salts can be commethylpiperidino) ethylmethylphenylamine salt bined with penicillin or its salts by neutraliza- 5 of penicillin G precipitates. The salt is sepation or metathetical reactions to form a sparingly rated, and dried in vacuo.

soluble penicillin salt, thereby affording a means The preparation of B-(Z-methylpiperidino) of precipitating penicillin from solution, and of ethylmethylphenylamine can be accomplished by purifying penicillin. Moreover, the novel penithe condensation of methyl aniline with 2- cillin salt can be utilized therapeutically. A pro- 10 methylpiperidinoethyl chloride in toluene solulonged penicillin blood level can be secured upon tion, in the presence of anhydrous potassium caradministering the salt parenterally by methods bonate. The acid addition salts of p-(2-methy1- known to the medical art. piperidino)ethylmethylphenylamine are pre- The base of the salt-forming compound of this pared by the usual methods, as, for example, by invention is repr d y th followin forinterreaction of equivalent amounts of the base mula: and the selected acid in inert solvent solution,

followed by removal of the solvent. 0 H OH I claim:

r- 1. A salt having as its components penicillin @N-CHr-OHa-N 0H, and p-(2 methylplperidino)ethylmethylphenylcur-0H, amine represented by the formula:

CH The following examples illustrate the prepaa ration of the novel salt of this invention: N Q

Example 1 To 3 g. of a solution of penicillin (e. g. a com- OHPCH mercial mixture of the several penicillins) dis- 2 The p 2 methy1piperidino) ethflmethyp solved in 50 m1. of amyl acetate are added 3 g. phenylamine ,11; of penicillin of 13 (2 methylpiperidino)ethylmethylphenylamine dissolved in 20 ml. of amyl acetate. The HARLEY RHODEHAMEL' mixture is cooled and stirred occasionally whereupon the B (2 methylpiperidino)ethy1methy1 References Cited in the file of th1s patent phenylamine salt of penicillin precipitates. The UNITED STATES PATENTS salt is isolated as by decantation or filtration, and Number Name t d i d n vacuo- 2,579,185 Granatek Dec. 18, 1951 Example 2 2,585,239 Granatek Feb. 12, 1952 To an aqueous solution of 0.3 g. of the potas- OTHER REFERENCES sium salt of penicillin G in 1.8 ml. of water is 40 British Report CMRFBr. 234 (PB 79,927), Deadded a solution of 0.3 g. of fl-(Z-methylpipericember 5, 1947, p. 3. 

1. A SALT HAVING AS ITS COMPONENTS PENICILLIN AND B-(2 - METHYLPIPERIDINO) ETHYLMETHYLPHENYLAMINE REPRESENTED BY THE FORMULA: 